Adjuvant and concurrent temozolomide for 1p/19q non-co-deleted anaplastic glioma (CATNON; EORTC study 26053-22054): second interim analysis of a randomised, open-label, phase 3 study

Bent, Martin J. van den; Tesileanu, C. Mircea S.; Wick, Wolfgang; Sanson, Marc; Brandes, Alba Ariela; Clément, Paul M.; Erridge, S. C.; Vogelbaum, Michael A.; Nowak, Anna K.; Baurain, J.; Mason, Warren P.; Wheeler, Helen; Chinot, Olivier; Gill, Sanjeev; Griffin, Matthew; Rogers, Leland; Taal, Walter; Rudà, Roberta; Weller, Michael; McBain, Catherine; Reijneveld, Jaap C.; Enting, Roelien H.; Caparrotti, Francesca; Lesimple, Thierry; Clenton, Susan; Gijtenbeek, Anja; Lim, Elizabeth; Herrlinger, Ulrich; Hau, Peter; Dhermain, Frédéric; Heer, Iris de; Aldape, Kenneth; Jenkins, Robert B.; Dubbink, Hendrikus J.; Kros, Johan M.; Wesseling, Pieter; Nuyens, Sarah; Golfinopoulos, Vassilis; Gorlia, Thierry; French, Pim J.; Baumert, Brigitta G.

doi:10.1016/s1470-2045(21)00090-5

Cited by 155 publications

(84 citation statements)

References 32 publications

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“…However, its role in IDHwt astrocytoma with pTERTmut is less well established. A subgroup analysis of the CATNON trial with 154 IDHwt astrocytoma with molecular features of glioblastoma showed that MGMT promotor methylation was prognostic for overall survival but not predictive for temozolomide chemotherapy in this cohort [ 7 ]. Data from the NOA-04 trial demonstrated the positive predictive value of MGMT promotor methylation in IDHwt astrocytomas WHO grade III but did not test for molecular features of glioblastoma like TERT promotor mutation [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

“…Methylation of the promotor region of the O6-methylguanine-DNA-methlytransferase (MGMT) gene is another molecular marker associated with favourable prognosis and response to alkylating chemotherapy in glioblastoma [ 5 , 6 ]. In the prospective CATNON trial (which compares radiotherapy with or without chemotherapy), a subgroup analysis of IDHwt astrocytoma with molecular features of glioblastoma demonstrated improved survival for tumors with MGMT promotor methylation (but surprisingly did not find evidence for beneficial effects of alkylating chemotherapy among methylated tumors) [ 7 ]. We recently reported on a large cohort of gliomas WHO grade II, and found that a higher number of methylated CpG sites within the MGMT promotor region also represents a positive prognostic factor for outcome in gliomas of lower grades [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Extent, pattern, and prognostic value of MGMT promotor methylation: does it differ between glioblastoma and IDH-wildtype/TERT-mutated astrocytoma?

et al. 2021

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Introduction The cIMPACT-NOW update 6 first introduced glioblastoma diagnosis based on the combination of IDH-wildtype (IDHwt) status and TERT promotor mutation (pTERTmut). In glioblastoma as defined by histopathology according to the WHO 2016 classification, MGMT promotor status is associated with outcome. Whether this is also true in glioblastoma defined by molecular markers is yet unclear. Methods We searched the institutional database for patients with: (1) glioblastoma defined by histopathology; and (2) IDHwt astrocytoma with pTERTmut. MGMT promotor methylation was analysed using methylation-specific PCR and Sanger sequencing of CpG sites within the MGMT promotor region. Results We identified 224 patients with glioblastoma diagnosed based on histopathology, and 54 patients with IDHwt astrocytoma with pTERTmut (19 astrocytomas WHO grade II and 38 astrocytomas WHO grade III). There was no difference in the number of MGMT methylated tumors between the two cohorts as determined per PCR, and also neither the number nor the pattern of methylated CpG sites differed as determined per Sanger sequencing. Progression-free (PFS) and overall survival (OS) was similar between the two cohorts when treated with radio- or chemotherapy. In both cohorts, higher numbers of methylated CpG sites were associated with favourable outcome. Conclusions Extent and pattern of methylated CpG sites are similar in glioblastoma and IDHwt astrocytoma with pTERTmut. In both tumor entities, higher numbers of methylated CpG sites appear associated with more favourable outcome. Evaluation in larger prospective cohorts is warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Extent, pattern, and prognostic value of MGMT promotor methylation: does it differ between glioblastoma and IDH-wildtype/TERT-mutated astrocytoma?

et al. 2021

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“…If this assumption would hold true when evaluated in prospective clinical trials is unclear, and no definitive treatment recommendation can be made at this point based on the findings from our study. Particularly, molecular markers will need to be considered when making treatment decisions 19 . However, prior prospective studies have demonstrated that if overall survival is prioritized, radiochemotherapy might be recommended in patients with glioma WHO grade 2 2 , 19 , 20 .…”

Section: Discussionmentioning

confidence: 99%

“…Particularly, molecular markers will need to be considered when making treatment decisions 19 . However, prior prospective studies have demonstrated that if overall survival is prioritized, radiochemotherapy might be recommended in patients with glioma WHO grade 2 2 , 19 , 20 . We did not find a significant association of use of radiochemotherapy and outcome in our cohort, potentially due to the small sample size of only 19 patients treated with radiochemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Subventricular zone involvement is associated with worse outcome in glioma WHO grade 2 depending on molecular markers

Karschnia

Weller

Blobner

et al. 2021

Sci Rep

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Neural stem cells within the subventricular zone were identified as cells of origin driving growth of high-grade gliomas, and anatomical involvement of the subventricular zone has been associated with an inferior clinical outcome. Whether the association between poor outcome and subventricular zone involvement also applies to glioma of lower grades is unclear. We therefore analysed a retrospective cohort of 182 patients with glioma grade 2 (according to the WHO 2016 classification) including 78 individuals (43%) with subventricular zone involvement. Patients with and without subventricular zone involvement did not differ in regard to demographics, histopathology, and molecular markers. Notably, subventricular zone involvement was a negative prognostic marker for malignant progression and overall survival on uni- and multivariate analysis. When patients were stratified according to the cIMPACT-NOW update 6, subventricular zone involvement was negatively associated with outcome in IDH-wildtype astrocytomas and 1p19q-codeleted oligodendrogliomas but not in IDH-mutant astrocytomas. Collectively, subventricular zone involvement may represent a risk factor for worse outcome in glioma WHO grade 2 depending on the molecular tumor signature. The present data confirm the relevance of molecular glioma classifications as proposed by the cIMPACT-NOW update 6. These findings warrant evaluation in prospective cohorts.

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“…It has been shown that patients with IDH1 and IDH2 mutated gliomas have better survival rates than patients with IDH wild type tumors ( 1 , 5 ). Recent studies demonstrated that IDH mutations in glioma predict the response to chemotherapy in anaplastic glioma ( 6 ). Hence, the detection of 2HG in IDH-mutated gliomas can aid in the diagnosis and treatment planning of glioma patients.…”

Section: Introductionmentioning

confidence: 99%

Comparison of 2-Hydroxyglutarate Detection With sLASER and MEGA-sLASER at 7T

et al. 2021

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The onco-metabolite 2-hydroxyglutarate (2HG), a biomarker of IDH-mutant gliomas, can be detected with 1H MR spectroscopy (1H-MRS). Recent studies showed measurements of 2HG at 7T with substantial gain in signal to noise ratio (SNR) and spectral resolution, offering higher specificity and sensitivity for 2HG detection. In this study, we assessed the sensitivity of semi-localized by adiabatic selective refocusing (sLASER) and J-difference MEsher-GArwood-semi-LASER (MEGA-sLASER) for 2HG detection at 7T. We performed spectral editing at long TE using a TE-optimized sLASER sequence (110 ms) and J-difference spectroscopy using MEGA-sLASER (TE = 74ms) in phantoms with different 2HG concentrations to assess the sensitivity of 2HG detection. The robustness of the methods against B0 inhomogeneity was investigated. Moreover, the performance of these two techniques was evaluated in four patients with IDH1-mutated glioma. In contrary to MEGA-sLASER, sLASER was able to detect 2HG concentration as low as 0.5 mM. In case of a composite phantom containing 2HG with overlapping metabolites, MEGA-sLASER provided a clean 2HG signal with higher fitting reliability (lower %CRLB). The results demonstrate that sLASER is more robust against field inhomogeneities and experimental or motion-related artifacts which promotes to adopt sLASER in clinical implementations.

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Adjuvant and concurrent temozolomide for 1p/19q non-co-deleted anaplastic glioma (CATNON; EORTC study 26053-22054): second interim analysis of a randomised, open-label, phase 3 study

Cited by 155 publications

References 32 publications

Extent, pattern, and prognostic value of MGMT promotor methylation: does it differ between glioblastoma and IDH-wildtype/TERT-mutated astrocytoma?

Extent, pattern, and prognostic value of MGMT promotor methylation: does it differ between glioblastoma and IDH-wildtype/TERT-mutated astrocytoma?

Subventricular zone involvement is associated with worse outcome in glioma WHO grade 2 depending on molecular markers

Comparison of 2-Hydroxyglutarate Detection With sLASER and MEGA-sLASER at 7T

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